The Iron Scale: Factors Tipping Towards Overload

Some of us may have grown up thinking that spinach is a good source of iron, but this isn’t exactly true. It’s been said that a report from the 1800’s mistakenly claimed that the vegetable has 10 times more iron than it actually has. It’s also known today that spinach contains the molecule oxalic acid, which can inhibit the absorption of iron. The amount of iron in spinach is on par with other dark, leafy green vegetables.
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Popeye’s love for spinach was once a symbol of humans’ need for iron and it’s true that many individuals are at risk for anemia, especially young children and pre-menopausal women. For this reason a number of countries market iron-fortified foods (a single serving of Post Grape-Nuts provides 90 percent of the daily dose of iron) and many multivitamins contain iron.

But while all humans need iron to survive, some people need less than others. Roughly one in 300 people with European ancestry has a genetic condition called hereditary hemochromatosis (he-mo-kro-mah-TOE-sis) that poses a risk for accumulating too much iron. Excessive iron can cause serious damage to organs and lead to liver disease, arthritis, and heart problems. This condition is recessive, meaning that you must inherit a bad gene from each parent to end up with the disorder.

In 1996 scientists identified the genetic defect underlying most forms of hereditary hemochromatosis — the C282Y mutation in the HFE gene that’s found in one in 10 people with European ancestry. As the years went on additional mutations in the HFE gene were identified including the very common but less severe H63D variant, found in one in five individuals, and the relatively mild S65C, which is carried by about one to two percent of people. These mutations are thought to interrupt the process by which the body regulates iron stores, something that is critical for optimal health.

(The rates above are for people with European ancestry. Hereditary hemochromatosis caused by mutations in the HFE gene is much rarer in Asian and African populations.)

Although finding the primary cause of “the most common genetic disease” was a breakthrough, it also laid the groundwork for a new medical mystery: only a small fraction of people with two HFE mutations ever develop serious complications as a result of iron overload. The advent of genetic testing in the late 1990’s allowed people of a variety of ages — both symptomatic and asymptomatic — to be screened for hereditary hemochromatosis and researchers quickly noted that although having two mutations seemed to elevate iron markers in the blood, most individuals never displayed more serious symptoms like liver disease and arthritis.

It’s not totally clear why some people with a genetic diagnosis of hereditary hemochromatosis go on to develop serious complications while others skate through life without problems, but numerous factors are likely at work. Iron accumulates in the body over time and thus age plays a big role. Sex is important since pre-menopausal women have a natural way of ridding the body of iron through monthly periods. It’s possible, though not yet proven, that additional genetic changes could be playing a role and thus it’s important to consider a person’s family history of the disease.

There’s also evidence that prevention through diet and lifestyle can be important. A withdrawal of iron fortification of flour in Sweden appears to be good news for people with hereditary hemochromatosis, but the question remains whether this benefit outweighs the risk it may pose to those with anemia. Alcohol is already tied to liver disease and when paired with hemochromatosis it can be even worse — a study in Australia showed that people with hemochromatosis who drank more than 60 grams of alcohol per day (about 2 ounces) were roughly nine times more likely to develop cirrhosis of the liver compared to those who drank less.

Editor’s note: Pending an FDA decision, 23andMe no longer offers new customers access to health reports referred to in this post. Customers who purchased prior to November 22, 2013 will still be able to see their health reports, but those who purchased after that time will not. Those customers will have access to ancestry information as well as access to their uninterpreted raw data.

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